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    MEFV Gene

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    Submitted by: Lily Guo
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    MEFV, pyrin innate immunity regulator

    1. Introduction

    The MEFV gene provides instructions for making a protein called pyrin (also known as marenostrin). Although pyrin's function is not fully understood, it likely assists in keeping the inflammation process under control. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body stops the inflammatory response to prevent damage to its own cells and tissues.

    Pyrin is produced in certain white blood cells (neutrophils, eosinophils, and monocytes) that play a role in inflammation and in fighting infection. Pyrin may direct the migration of white blood cells to sites of inflammation and stop or slow the inflammatory response when it is no longer needed. Pyrin also interacts with other molecules involved in fighting infection and in the inflammatory response. Research indicates that pyrin helps regulate inflammation by interacting with the cytoskeleton, the structural framework that helps to define the shape, size, and movement of a cell.

    2. Health Conditions Related to Genetic Changes

    2.1. Familial Mediterranean fever

    More than 80 MEFV gene mutations that cause familial Mediterranean fever have been identified. A few mutations delete small amounts of DNA from the MEFV gene, which can lead to an abnormally small, nonfunctional protein. Most MEFV gene mutations, however, change one of the protein building blocks (amino acids) used to make pyrin. The most common mutation replaces the amino acid methionine with the amino acid valine at protein position 694 (written as Met694Val or M694V). Among people with familial Mediterranean fever, this particular mutation is also associated with an increased risk of developing amyloidosis, a complication in which abnormal protein deposits can lead to kidney failure. Some evidence suggests that variations in another gene, called SAA1, can further modify the risk of developing amyloidosis among people with the M694V mutation.

    MEFV gene mutations lead to reduced amounts of pyrin or a malformed pyrin protein that cannot function properly. As a result, pyrin cannot perform its presumed role in controlling inflammation, leading to an inappropriate or prolonged inflammatory response. Fever and inflammation in the abdomen, chest, joints, or skin are signs of familial Mediterranean fever.

    3. Other Names for This Gene

    • FMF
    • marenostrin
    • Mediterranean fever
    • MEF
    • MEFV_HUMAN
    • MRST
    • pyrin
    • TRIM20

    The entry is from https://medlineplus.gov/genetics/gene/mefv

    References

    1. Aksentijevich I, Torosyan Y, Samuels J, Centola M, Pras E, Chae JJ, Oddoux C, Wood G, Azzaro MP, Palumbo G, Giustolisi R, Pras M, Ostrer H, Kastner DL.Mutation and haplotype studies of familial Mediterranean fever reveal newancestral relationships and evidence for a high carrier frequency with reducedpenetrance in the Ashkenazi Jewish population. Am J Hum Genet. 1999Apr;64(4):949-62.
    2. Bakkaloglu A. Familial Mediterranean fever. Pediatr Nephrol. 2003Sep;18(9):853-9.
    3. Chae JJ, Wood G, Masters SL, Richard K, Park G, Smith BJ, Kastner DL. TheB30.2 domain of pyrin, the familial Mediterranean fever protein, interactsdirectly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci U SA. 2006 Jun 27;103(26):9982-7.
    4. Delibaş A, Oner A, Balci B, Demircin G, Bulbul M, Bek K, Erdoğan O, Baysun S, Yilmaz E. Genetic risk factors of amyloidogenesis in familial Mediterraneanfever. Am J Nephrol. 2005 Sep-Oct;25(5):434-40.
    5. Gershoni-Baruch R, Brik R, Zacks N, Shinawi M, Lidar M, Livneh A. Thecontribution of genotypes at the MEFV and SAA1 loci to amyloidosis and diseaseseverity in patients with familial Mediterranean fever. Arthritis Rheum. 2003Apr;48(4):1149-55.
    6. Mansfield E, Chae JJ, Komarow HD, Brotz TM, Frucht DM, Aksentijevich I,Kastner DL. The familial Mediterranean fever protein, pyrin, associates withmicrotubules and colocalizes with actin filaments. Blood. 2001 Aug 1;98(3):851-9.
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    8. Mikula M, Buller A, Sun W, Strom CM. Prevalence of known mutations in thefamilial Mediterranean fever gene (MEFV) in various carrier screeningpopulations. Genet Med. 2008 May;10(5):349-52. doi: 10.1097/GIM.0b013e3181723cc8.
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    10. Notarnicola C, Didelot MN, Koné-Paut I, Seguret F, Demaille J, Touitou I.Reduced MEFV messenger RNA expression in patients with familial Mediterraneanfever. Arthritis Rheum. 2002 Oct;46(10):2785-93.
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    13. Ross JJ. Goats, germs, and fever: Are the pyrin mutations responsible forfamilial Mediterranean fever protective against Brucellosis? Med Hypotheses.2007;68(3):499-501.
    14. Stoffman N, Magal N, Shohat T, Lotan R, Koman S, Oron A, Danon Y, Halpern GJ, Lifshitz Y, Shohat M. Higher than expected carrier rates for familialMediterranean fever in various Jewish ethnic groups. Eur J Hum Genet. 2000Apr;8(4):307-10.
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    16. Yepiskoposyan L, Harutyunyan A. Population genetics of familial Mediterranean fever: a review. Eur J Hum Genet. 2007 Sep;15(9):911-6.
    17. Yu JW, Fernandes-Alnemri T, Datta P, Wu J, Juliana C, Solorzano L, McCormickM, Zhang Z, Alnemri ES. Pyrin activates the ASC pyroptosome in response toengagement by autoinflammatory PSTPIP1 mutants. Mol Cell. 2007 Oct26;28(2):214-27.
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